Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity. In this end-of-study analysis, the median follow-up was 10.3 years. Compared with standard adjuvant chemotherapy, dose-dense treatment improved breast cancer recurrence-free survival (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.98]; P = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; P = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; P = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; P = .109). To our knowledge, this is the first trial that confirms the benefit of a dose-dense regimen over a control regimen containing docetaxel once every 3 weeks.

Trial registration: ClinicalTrials.gov NCT00798070.

FIG 1.

Cumulative incidence curves of efficacy end points in the intention-to-treat population. Cumulative incidence curves and 10-year event rates for breast cancer (A) relapse-free survival events, (B) event-free survival events, (C) distant disease-free survival events, and (D) overall survival events. Log-rank test refers to comparisons of crude, unadjusted event rates. D, docetaxel; EC, epirubicin, cyclophosphamide; FEC, fluorouracil, epirubicin, cyclophosphamide; tDD, tailored dose dense.

FIG 2.

Subgroup analysis of breast cancer-free survival events. The size of each box is proportional to the size of the respective subgroup. Hormone receptor–positive includes estrogen receptor– and/or progesterone receptor–positive patients; hormone receptor–negative includes estrogen and progesterone receptor–negative patients. D, docetaxel; EC, epirubicin, cyclophosphamide; FEC, fluorouracil, epirubicin, cyclophosphamide; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; tDD, tailored dose dense.